CRISPR/Cas9 screens implicate RARA and SPNS1 in doxorubicin cardiotoxicity | JACC: CardioOncology

Researchers used genome‑wide CRISPR/Cas9 loss‑of‑function screens in cardiomyocytes to identify RARA and SPNS1 as key modulators of doxorubicin cardiotoxicity, highlighting pathways that influence both injury susceptibility and intracellular drug handling. Activation of RARA reduced toxicity without impairing anticancer effects, while SPNS1 loss caused harmful drug accumulation, offering new mechanistic insights and potential therapeutic targets.